World Journal of
Gastroenterology
World J Gastroenterol 2017 May 7; 23(17): 3011-3194
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
S
EDITORIAL
3011 Esophagitis and its causes: Who is “guilty” when acid is found “not guilty”? Grossi L, Ciccaglione AF, Marzio L
3017 Checkpoint inhibitors in gastrointestinal cancers: Expectations and reality Kourie HR, Tabchi S, Ghosn M
FRONTIER
3022 BRAF inhibitor treatment of melanoma causing colonic polyps: An alternative hypothesis Kelleher FC, Callaghan G, Gallagher C, O’Sullivan H
REVIEW
3030 Genes, emotions and gut microbiota: The next frontier for the gastroenterologist Panduro A, Rivera-Iñiguez I, Sepulveda-Villegas M, Roman S
3043 Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury Qin CC, Liu YN, Hu Y, Yang Y, Chen Z
ORIGINAL ARTICLE
Basic Study3053 CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma Xin Q, Zhang N, Yu HB, Zhang Q, Cui YF, Zhang CS, Ma Z, Yang Y, Liu W
3066 Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression
Yang TW, Gao YH, Ma SY, Wu Q, Li ZF Retrospective Cohort Study
3077 Pancreaticoduodenectomy in patients ≥ 75 years of age: Are there any differences with other age ranges in oncological and surgical outcomes? Results from a tertiary referral center
Paiella S, De Pastena M, Pollini T, Zancan G, Ciprani D, De Marchi G, Landoni L, Esposito A, Casetti L, Malleo G, Marchegiani G, Tuveri M, Marrano E, Maggino L, Secchettin E, Bonamini D, Bassi C, Salvia R
Retrospective Study
3084 New flexible endoscopic controlled stapler technique for the treatment of Zenker’s diverticulum: A case series
Wilmsen J, Baumbach R, Stüker D, Weingart V, Neser F, Gölder SK, Pfundstein C, Nötzel EC, Rösch T, Faiss S
Contents
Weekly Volume 23 Number 17 May 7, 2017
May 7, 2017|Volume 23|ssue 17|
Contents
Volume 23 Number 17 May 7, 2017
World Journal of Gastroenterology
3092 Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors
Paiella S, Impellizzeri H, Zanolin E, Marchegiani G, Miotto M, Malpaga A, De Robertis R, D'Onofrio M, Rusev B, Capelli P, Cingarlini S, Butturini G, Davì MV, Amodio A, Bassi C, Scarpa A, Salvia R, Landoni L
3099 Octogenarian liver grafts: Is their use for transplant currently justified?
Jiménez-Romero C, Cambra F, Caso O, Manrique A, Calvo J, Marcacuzco A, Rioja P, Lora D, Justo I
3111 Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma
Hao Y, Numata K, Ishii T, Fukuda H, Maeda S, Nakano M, Tanaka K
3122 Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/ hepatic vein tumor thrombosis
Li SH, Wang QX, Yang ZY, Jiang W, Li C, Sun P, Wei W, Shi M, Guo RP Clinical Trials Study
3133 Diagnostic value of gadobenate dimeglumine-enhanced hepatocyte-phase magnetic resonance imaging in evaluating hepatic fibrosis and hepatitis
Li XM, Chen Z, Xiao EH, Shang QL, Ma C Observational Study
3142 Consequences of metabolic syndrome on postoperative outcomes after pancreaticoduodenectomy Zarzavadjian Le Bian A, Fuks D, Chopinet S, Gaujoux S, Cesaretti M, Costi R, Belgaumkar AP, Smadja C, Gayet B 3150 Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity
of the non-alcoholic fatty liver disease
Gelli C, Tarocchi M, Abenavoli L, Di Renzo L, Galli A, De Lorenzo A Prospective Study
3163 Cost-effectiveness of enhanced liver fibrosis test to assess liver fibrosis in chronic hepatitis C virus and alcoholic liver disease patients
Soto M, Sampietro-Colom L, Lasalvia L, Mira A, Jiménez W, Navasa M
3174 Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett’s esophagus
Baldaque-Silva F, Vieth M, Debel M, Håkanson B, Thorell A, Lunet N, Song H, Mascarenhas-Saraiva M, Pereira G, Lundell L, Marschall HU
3184 Comparison of endoscopic ultrasound, computed tomography and magnetic resonance imaging in assessment of detailed structures of pancreatic cystic neoplasms
Du C, Chai NL, Linghu EQ, Li HK, Sun LH, Jiang L, Wang XD, Tang P, Yang J
May 7, 2017|Volume 23|ssue 17|
Contents
Volume 23 Number 17 May 7, 2017
World Journal of Gastroenterology
May 7, 2017|Volume 23|ssue 17|
WJG|www.wjgnet.com
LETTER TO THE EDITOR
3193 Efficacy and safety of stellate ganglion block in chronic ulcerative colitis Lipov E, Candido K
NAME OF JOURNAL
World Journal of Gastroenterology
ISSN ISSN 1007-9327 (print) ISSN 2219-2840 (online) LAUNCH DATE October 1, 1995 FREQUENCY Weekly EDITORS-IN-CHIEF
Damian Garcia-Olmo, MD, PhD, Doctor, Profes-sor, Surgeon, Department of Surgery, Universidad
Autonoma de Madrid; Department of General Sur-gery, Fundacion Jimenez Diaz University Hospital, Madrid 28040, Spain
Stephen C Strom, PhD, Professor, Department of
Laboratory Medicine, Division of Pathology, Karo-linska Institutet, Stockholm 141-86, Sweden
Andrzej S Tarnawski, MD, PhD, DSc (Med), Professor of Medicine, Chief Gastroenterology, VA
Long Beach Health Care System, University of Cali-fornia, Irvine, CA, 5901 E. Seventh Str., Long Beach,
CA 90822, United States EDITORIAL BOARD MEMBERS
All editorial board members resources online at http:// www.wjgnet.com/1007-9327/editorialboard.htm EDITORIAL OFFICE
Jin-Lei Wang, Director Yuan Qi, Vice Director Ze-Mao Gong, Vice Director
World Journal of Gastroenterology
Baishideng Publishing Group Inc 7901 Stoneridge Drive, Suite 501, Pleasanton, CA 94588, USA Telephone: +1-925-2238242 Fax: +1-925-2238243
E-mail: editorialoffice@wjgnet.com
Help Desk: http://www.f6publishing.com/helpdesk http://www.wjgnet.com
PUBLISHER
Baishideng Publishing Group Inc 7901 Stoneridge Drive, Suite 501, Pleasanton, CA 94588, USA Telephone: +1-925-2238242 Fax: +1-925-2238243 E-mail: bpgoffice@wjgnet.com
Help Desk: http://www.f6publishing.com/helpdesk
Contents
EDITORS FOR
THIS ISSUE
Responsible Assistant Editor: Xiang Li Responsible Science Editor: Ze-Mao Gong Responsible Electronic Editor: Fen-Fen Zhang Proofing Editorial Office Director: Jin-Lei Wang Proofing Editor-in-Chief: Lian-Sheng Ma
http://www.wjgnet.com PUBLICATION DATE May 7, 2017 COPYRIGHT
© 2017 Baishideng Publishing Group Inc. Articles pub-lished by this Open-Access journal are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.
SPECIAL STATEMENT
All articles published in journals owned by the Baishideng Publishing Group (BPG) represent the views and opin-ions of their authors, and not the views, opinopin-ions or policies of the BPG, except where otherwise explicitly indicated.
INSTRUCTIONS TO AUTHORS
Full instructions are available online at http://www. wjgnet.com/bpg/gerinfo/204
ONLINE SUBMISSION http://www.f6publishing.com
World Journal of Gastroenterology
Volume 23 Number 17 May 7, 2017
Editorial board member of World Journal of Gastroenterology, Maurizio Degiuli, FRCS (Gen Surg), MD, PhD, Associate Professor, Head, Department of Oncology, University of Turin, School of Medicine, San Luigi University Hospital, Orbassano- Turin 10043, ItalyWorld Journal of Gastroenterology (World J Gastroenterol, WJG, print ISSN 1007-9327, online
ISSN 2219-2840, DOI: 10.3748) is a peer-reviewed open access journal. WJG was
estab-lished on October 1, 1995. It is pubestab-lished weekly on the 7th, 14th, 21st, and 28th each month.
The WJG Editorial Board consists of 1375 experts in gastroenterology and hepatology
from 68 countries.
The primary task of WJG is to rapidly publish high-quality original articles, reviews,
and commentaries in the fields of gastroenterology, hepatology, gastrointestinal endos-copy, gastrointestinal surgery, hepatobiliary surgery, gastrointestinal oncology, gastroin-testinal radiation oncology, gastroingastroin-testinal imaging, gastroingastroin-testinal interventional ther-apy, gastrointestinal infectious diseases, gastrointestinal pharmacology, gastrointestinal pathophysiology, gastrointestinal pathology, evidence-based medicine in gastroenterol-ogy, pancreatolgastroenterol-ogy, gastrointestinal laboratory medicine, gastrointestinal molecular biol-ogy, gastrointestinal immunolbiol-ogy, gastrointestinal microbiolbiol-ogy, gastrointestinal genetics, gastrointestinal translational medicine, gastrointestinal diagnostics, and gastrointestinal therapeutics. WJG is dedicated to become an influential and prestigious journal in
gas-troenterology and hepatology, to promote the development of above disciplines, and to improve the diagnostic and therapeutic skill and expertise of clinicians.
World Journal of Gastroenterology (WJG) is now indexed in Current Contents®/Clinical Medicine,
Science Citation Index Expanded (also known as SciSearch®), Journal Citation Reports®, Index
Medicus, MEDLINE, PubMed, PubMed Central, Digital Object Identifier, and Directory of Open Access Journals. The 2015 edition of Journal Citation Reports® released by Thomson
Reuters (ISI) cites the 2015 impact factor for WJG as 2.787 (5-year impact factor: 2.848),
rank-ing WJG as 38 among 78 journals in gastroenterology and hepatology (quartile in category Q2).
I-IX Editorial Board
ABOUT COVER
INDEXING/ABSTRACTING
AIMS AND SCOPE
FLYLEAF
V May 7, 2017|Volume 23|ssue 17|
Chiara Gelli, Laura Di Renzo, Antonino De Lorenzo,Division of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 0133 Rome, Italy
Chiara Gelli, Mirko Tarocchi, Andrea Galli,Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50134 Florence, Italy
Ludovico Abenavoli, Department of Health Sciences, University Magna Graecia, Campus Germaneto, 88100 Catanzaro, Italy Author contributions: Gelli C and Tarocchi M contributed equally to this work; Gelli C and Tarocchi M designed and performed the research; Gelli C wrote the manuscript; Tarocchi M, Di Renzo L, De Lorenzo A, Galli A and Abenavoli L reviewed and edited the manuscript; all authors read and approved the manuscript.
Supported by Fondo per gli Investimenti della Ricerca di Base, No. RBAP10MY35_002; Ente Cassa di Risparmio di Firenze; and FiorGen ONLUS to Galli A.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee “Centro, RC” n. 30.11.02.2016.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors confirm that this article content has no conflict of interest.
Data sharing statement: Dataset available from the corresponding author at mirko.tarocchi@unifi.it.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this
work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/
Manuscript source: Invited manuscript
Correspondence to: Dr. Mirko Tarocchi, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence,
Italy. mirko.tarocchi@unifi.it Telephone: +39-55-2758115 Fax: +39-55-2758119 Received: December 20, 2016
Peer-review started: December 22, 2016 First decision: January 10, 2017
Revised: February 13, 2017 Accepted: April 13, 2017 Article in press: April 13, 2017 Published online: May 7, 2017
Abstract
AIM
To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease (NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.
METHODS
Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention (based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting (about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed
3150 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
ORIGINAL ARTICLE
Effect of a counseling-supported treatment with the
Mediterranean diet and physical activity on the severity of
the non-alcoholic fatty liver disease
Observational Study
Chiara Gelli, Mirko Tarocchi, Ludovico Abenavoli, Laura Di Renzo, Andrea Galli, Antonino De Lorenzo
Submit a Manuscript: http://www.f6publishing.com DOI: 10.3748/wjg.v23.i17.3150
World J Gastroenterol 2017 May 7; 23(17): 3150-3162 ISSN 1007-9327 (print) ISSN 2219-2840 (online)
by ultrasound (US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid- and end-interventions and US was repeated at end-intervention.
RESULTS
The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients (20%). At the end of the treatment the end-point concerning the weight (
i.e.
, a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients (i.e.
, 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme (altered values reduced from 67% down to 11%). Several parameters,i.e.
, BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/ HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement (P
< 0.01) between baseline and end-treatment.
CONCLUSION
Outcomes of this study further strengthen the hypo-thesis that MedDiet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.
Key words: alcoholic fatty liver disease;
Non-alcoholic steatohepatitis; Mediterranean diet; Metabolic syndrome; Therapeutic approach; Counseling; Diet; Life-style
© The Author(s) 2017. Published by Baishideng Publishing
Group Inc. All rights reserved.
Core tip: Most recent advances in the management
and treatment of Non-alcoholic fatty liver disease (NAFLD) show that a multifaceted approach is likely to achieve the best outcomes. Our study evaluates the effectiveness of 6-mo multidisciplinary approach jointly carried out by a gastroenterologist and a nutritionist with counseling license. The approach was effective on the reduction of NAFLD severity, weight, anthropometric indexes, cardiovascular disease risk factors and the normalization of metabolic index, as well as liver enzymes. This study strengthens the hypothesis that MedDiet and more active lifestyle can be considered a safe therapeutic approach for reducing severity of NAFLD.
Gelli C, Tarocchi M, Abenavoli L, Di Renzo L, Galli A, De Lorenzo A. Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease. World J Gastroenterol 2017; 23(17): 3150-3162 Available from: URL: http://www.wjgnet.
com/1007-9327/full/v23/i17/3150.htm DOI: http://dx.doi. org/10.3748/wjg.v23.i17.3150
INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) is a relevant issue in public health because represents a major cause of chronic liver diseases worldwide. Approximately 20% to 30% of adult population has NAFLD, making it the most common liver disease in developed countries[1,2].
NAFLD is the result of fat accumulation in the liver (with fat representing more than 5% of whole liver weight) in absence of excessive alcohol consumption (usually evaluated using thresholds of 20 and 30 g/d for women and men respectively[3].
NAFLD includes two pathologically distinct conditions with different prognoses: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); the latter covers a wide spectrum of disease severity, including fibrosis and cirrhosis and promoting hepatocellular carcinoma development[4].
NAFLD is a multifactorial disease and the exact mechanism is unknown. It is usually associated to one or more conditions that contribute to the meta-bolic syndrome (MS) (diabetes mellitus, obesity, hypertension, and hyperlipidemia) and therefore is considered as its hepatic manifestation[5-9].
Several therapeutic interventions for NAFLD have been proposed over the last decades but any of these proved to be safe and effective[10,11]. Among
therapeutic interventions there are weight reduction (e.g., low-calorie diet, exercise and bariatric surgery), insulin sensitizer agents and incretins, lipid lowering drugs (e.g., statins), antioxidants (e.g., vitamin E) and treatment of vitamin D3 deficiency[12]. Pharmacological
therapies have not been always successful in reducing liver steatosis or inflammation[12,13]. On the other
hand, other drugs, such as thiazolidinediones, have some success in improving liver histology but have undesirable side effects such as weight gain[14].
Epidemiological evidence suggests a tight relationship between unhealthy lifestyle (mainly related to diet and physical inactivity) and NAFLD (Zelber-Sagi et al[15],
2011) and therefore there is a general consensus on considering healthy diet and regular physical activity as the cornerstones in the treatment of NAFLD[4,12,16]. In
addition, these interventions have been demonstrated also effective for improving conditions of MS and the related risk of cardiovascular disease (CVD)[17].
So far several dietary models have been proposed for reducing severity and preventing NAFLD. Among these, the Mediterranean diet (MedDiet) can be considered one of the healthiest as its benefits are attributed to a lower incidence of chronic disease including CVD, obesity, cancers, and overall mortality demonstrating its safety, palatability and sustaina-bility[18]. According to several studies carried out during
3151 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
the last few years[19,20], the MedDiet resulted as the
most effective for inducing weight loss together with beneficial effects on all the risk factors associated with MS and NAFLD as demonstrated in several[21] state
that higher adherence to MedDiet seems to have a beneficial effect on the severity of disease in patients with NAFLD.
Increased routinary physical activity demonstrated to be beneficial in reducing the severity of NAFLD both associated to weight loss[22] or per se[23] and is well
known for its beneficial effects on reducing risks of developing components of MS[24]. Some studies also
showed that increased routinary physical activity[25] and
cardiorespiratory fitness[26] are inversely associated with
NAFLD.
For all these reasons, a structured programme aimed at lifestyle changes towards healthy diet (with a 7%-10% weight loss in overweight/obese patients) and routinary physical activity is the most advisable for the treatment of NAFLD[4].
Nonetheless, lifestyle modification is usually difficult to achieve and maintain, above all in the long term, for a variety of reasons[27,28]. In particular, many
patients have difficulty to find motivation to change their unhealthy lifestyle although most of them are well aware of the importance of healthy diet and habitual physical activity. Centis et al[29] report NAFLD cases have
scarce readiness to physical activity change, and 50% of cases were classified in either the precontemplation or contemplation stage of change, i.e., refractory to increase exercise.
For these reasons there, in order to increase the success of the approach laying on lifestyle change towards a healthy diet and habitual physical activity, there is the need to move from the traditional pres-criptive approach to an individualized, multidisciplinary, empowerment-based intervention, tailored on patients’ preferences.
In this study we tested the effectiveness of nutri-tional counseling on reduction of NAFLD severity, weight loss, metabolic and anthropometric indexes and liver enzymes. The approach was jointly carried out by a gastroenterologist and a nutritionist with counseling patent and was aimed at supporting patients to move toward a lifestyle including MedDiet-based dietary habits and regular physical activity.
MATERIALS AND METHODS
Study design and outcome measures
This observational study proposes a 6-mo interventions for treating patients with NAFLD. The approach is based on a clinical and a MedDiet-based dietary intervention carried out respectively by a gastroenterologist and a nutritionist with counseling license. The innovation of this approach is the use of the nutritional counseling to strengthen participants’ motivation and increase adherence to healthy lifestyle recommendations and,
at the same time, educating and promoting lifelong healthy eating habits.
Prospective participants underwent a thorough screening visit and a detailed analysis to asses clinical and health-related conditions, biochemistry, dietary habits, physical activity level, lifestyle and anthropometry. The nutritionist also provided patients with indications for drafting the food and physical activity diaries (including 3 weekdays and 1 weekend).
Eligible participants underwent a second meeting (after 1 wk) with the nutritionist who gather drafted food and physical activity diaries (then used to check and further refine the outcomes of the first interview) and deliver to the participants written resources containing the food pyramid, healthy eating guidelines and tips, basic information on portion size, examples to reduce food intake (maximum calorie reduction, 500 kcal/d) and dietary recommendations. These latter were specifically designed and tailored taking into account nutritional needs, diseases (if any), and other information and/or needs communicated during the first meeting and consisted of daily and weekly meal plans and suggestion for meals composition stimulating patients to self-arrange their diet according to the MedDiet. Within this meeting also starts the counseling process (see below).
During monthly meetings, carried out for the counseling process, the nutritionist also evaluates the adherence to the dietary recommendations, makes eventual adjustments, assesses anthropometry and assists participants in maintaining motivations.
Biochemistry was assessed at mid- and end-interventions (3 and 6 mo) and ultrasonography was repeated at end-intervention (6 mo).
The following end-points were set to assess the efficacy of the proposed approach: (1) reduction of at least 1 unit of steatosis grade; (2) A 7% weight reduction (in accordance to EASL-EASD-EASO, 2016[4])
or achievement/maintenance of normal weight; (3) Normalization or improvement of metabolic indexes [Total cholesterol (Tot-Chol), HDL-cholesterol, LDL-cholesterol, serum glucose, triglycerides (TG)]; and (4) normalization or improvement of ALT, AST, GGT.
Participant recruitment and eligibility
For this study were recruited 46 adult (26-71 years old) patients with recent (within the previous 6 mo) diagnosis of NAFLD, who visited the outpatient liver clinics of the at Clinical Gastroenterology Unit, University Hospital Careggi between February 2016 and August 2016.
The diagnosis was based on clinical, ultrasono-graphic and laboratory values, after exclusion of any other cause of chronic liver disease (hepatitis B and C virus, autoimmune and metabolic disease) and alcohol intake not exceeding 20 g/d (confirmed by relatives).
Participants were excluded if they: (1) refused or were unable to give informed consent to participate
3152 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
3153 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
and traditional, local, eco-friendly and biodiverse products.
Anthropometry, biochemistry and inflammatory markers
Weight, height, waist circumference, hip circumference, BMI were taken using standard procedures by the nutritionist.
Liver enzymes (AST, ALT, alkaline phosphatase, GGT), Tot-Chol, HDL-cholesterol, LDL-cholesterol, serum glucose, TG, insulin resistance index HOMA-Ir and QUICKI were acquired or calculated from medical records delivered by participants.
The following indexes related to NAFLD were also calculated: the Kotronen index and NAFLD liver fat score[33], the Fatty Liver Index (FLI)[34] and the
Visceral Adipose Index (VAI)[35]. Kotronen index is
used as predictor of liver fat percentage. NAFLD liver fat score allows identification of NAFLD using easily available clinical and laboratory data. FLI measures the probability of significant steatosis (values < 30 rule out and values ≥ 60 rule in fatty liver). VAI is an indicator of visceral fat associated with cardiometabolic risk.
In order to make an enlarged clinical and nutritional evaluation of participants were estimated some cardiovascular risk indexes [Tot-Chol/HDL, LDL/HDL, TG/HDL and atherogenic index of plasma (AIP)], systemic inflammation indexes [platelet to lymphocyte ratio (PLr) and neutrophil to lymphocyte ratio (NLr)], a marker of MS [lipid accumulation product (LAP)] and two indexes used to assess advanced liver fibrosis in patients with NAFLD (BArD and NAFLD).
Assessment of the adherence to the MedDiet
The level of adherence to the Mediterranean dietary pattern was evaluated using the Mediterranean Diet Score (MedDietScore) as defined by Panagiotakos
et al[36]. Briefly, for the score calculation, the
con-sumption of food items from 9 food groups (non-refined starchy food, potatoes, fruit, vegetables, legumes, fish, meat and meat products, poultry, and full fat dairy products), as well as olive oil, and alcoholic beverages, have to be taken into account. For each food item a score is assigned on the basis of the frequency of consumption. For food items close to the MedDiet the higher the frequency the higher the score and viceversa for food items that are away from the MedDiet. For further information, refer to Panagiotakos
et al[36].
Counseling process
The counseling is an ongoing process taking all the intervention’s duration and in each meeting the nutritionist and the patient discuss the opportunity to reevaluate goals and strategies for achieving set goals. During the counseling process the nutritionist and the patient work together to identify areas where change is needed, prioritize changes, and problem-solve as to how to make the changes.
in the study; (2) had evidence of advanced liver disease (cirrhosis, hepatocellular carcinoma); (3) had clinically relevant pathologies (e.g., pulmonary, gastro-intestinal, renal, metabolic, haematological, neurological, psychiatric, systemic or any acute infectious disease or signs of acute illness); and (4) had contraindications included bulimia nervosa, substance abuse, clinically significant depression, or current psychiatric care.
The study was approved by the appropriate Ethics Committee (“Centro, rC” 30.11.02.2016) and was carried out in accordance with the declaration of Helsinki[30]. All patients gave their written informed
consent before the recruitment.
Dietary intervention
The dietary intervention was based on the MedDiet which was firstly introduced and described by Keys
et al in “The Seven Countries Study”. After that study
several other studies confirmed the beneficial effects and outcomes of the MedDiet on the health mainly reducing mortality, cardiovascular disease risk factors and cancer (Sofi et al[18], 2010).
The MedDiet is based on a balanced use of foods rich in fiber, antioxidants and unsaturated fats, a healthy approach designed to reduce the consump-tion of animal fats and cholesterol in a diet with an appropriate balance between energy intake and ex-penditure[31]. Therefore the MedDiet is characterized
by high consumption of vegetables, fruits, non-refined cereals, legumes and potatoes, moderate consumption of fish and poultry and low consumption of full fat dairies, red meat and its products and homemade sweets. Olive oil is the basic source of fat used for food preparation and during consumption. Meals are often accompanied by low-to-moderate amounts of wine. The relationships between the macronutrient in the MedDiet is 55%-60% of carbohydrates of which 80% complex carbohydrates (bread, pasta, rice), 10%-15% of proteins about 60% of animal origin (especially white meat, fish), 25%-30% fat (mostly olive oil)[31].
The MedDiet has also a graphic representation which is typically a pyramid whose most updated version is described by[32]. The graphic representation
follows the previous pattern: at the base, food items that should sustain the diet and provide the highest energy intake, and at the upper levels, foods to be eaten in moderate amounts such as those of animal origin and/or rich in sugars and fats that should be eaten in moderation and some of them left for special occasions[32].
Along with recommendations regarding the pro-portion and frequency of food consumption, the incorporation of cultural and lifestyle elements is one of the innovations of the latest version of the pyramid. These concepts represented outside of the pyramid, but at its base, are: moderation, socialization, culinary activities, physical activity, adequate rest, seasonality
3154 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
In this study the counseling process was individually-tailored and consisted of 6 monthly 30-45 min face-to face meetings aimed face-to enhance internal motivation and facilitate behavior change concerning both diet and lifestyle (in terms of physical activity level). The techniques used were mainly: motivational interviewing, active listening and rogers/PNL/Gestalt techniques.
As far as dietary habits, patients were stimulated in order to strengthen their capability to successfully follow and adhered to the recommendations contained in written resources delivered and dietary intervention as described in the previous section.
The nutritionist initially explains to the patient that making dietary change should be a gradual process and that the truth challenge is not in making the initial dietary changes, but in maintaining them over the long term. The process may start with one or two easier dietary changes in the first few weeks and gradually make additional or more difficult changes over several weeks or months. In addition, factors affecting food decisions (ethnic background, religion, group affiliation, socioeconomic status) are taken into account during meetings.
The nutritionist and patient also set behavior-oriented goals together focusing on the behaviors needed to achieve the desired dietary change, not on an absolute value, such as achieving a certain body weight. Once the needed changes and goals have been identified, the patient and nutrition counselor think through potential problems that may arise (e.g., purchasing different foods, planning ahead for social events, or bringing special foods to work).
As far as the physical activity is concerned, the counseling approach was mainly used to stimulate patients to increase their physical activity. A motivational method instead of the common prescriptive one, was used to favor a more active lifestyle taking an incremental approach i.e., trying to increase the general level of activity throughout the day and every day up to a level sustainable and compatible with physical conditions and time available.
During the meetings patients and the nutritional counselor tried to set achievable goals tailored on the physical conditions of single patient. People with (very) limited physical activity level were stimulated to start identifying and putting in practice ways to increase their physical activity. For example, elder people and obese were stimulated to identify daily activities that could increase their physical activity (e.g., walking, riding the bike, get off the bus one stop earlier, walk up the stairs instead of taking the elevator, walk the dog, walk with their children, etc.). All patients without any physical constrain were stimulated to identify and take up/maintain regular physical activity. For these latter patients, the final goal was a habitual physical activity workload > 20 METs/h per week (corresponding to 3-h/wk moderate-intense physical activity) which was used in the study of Montesi et al[37].
Ultrasound assessment of NAFLD
Severity of NAFLD was assessed by ultrasound (US) (Ultrasound alpha 7, Hitachi Aloka Medical America, Inc.). The US results were interpreted always by the same investigator well experienced in performing and interpreting hepatic US and blinded to the clinical data. The sonographic findings that were specifically evaluated included the hepato-renal contrast, bright hepatic echoes, deep attenuation, vessel blurring and non-specific findings of heterogeneous echoes. The degree of steatosis during US was graded as ab-sent (0), mild (1), moderate (2) and severe (3). The liver image was assessed to be normal if the texture was homogenous, exhibited fine level echoes and isoechoic compared to the renal cortex and adequate visualization of the hepatic vessels and diaphragm (grade 0). Criteria for determining the degree of liver steatosis included: presence of bright echoes or increased hepato-renal contrast indicative of mild steatosis (grade 1); presence of both bright echoes and increased hepato-renal contrast as well as vessel blurring indicative of moderate steatosis (grade 2); severe steatosis was considered to be present when in addition to the criteria for moderate steatosis, there was evidence of posterior beam attenuation and non-visualization of the diaphragm (grade 3)[38].
Statistical analysis
Microsoft Office Excel 2007 and IBM SPSS Statistics for Windows 20.0.0 were used for all the statistical calculations. Continuous variables are presented as mean values ± SD, while categorical variables are presented as frequencies. Unpaired t-test (2-tail) was used to test differences between baseline, mid-treatment (3 mo) and end-mid-treatment (6 mo). Fisher’s distribution was used to assess significance of linear regression between steatosis grade and anthropometric, clinical and metabolic parameters at baseline (BL), mid-treatment (3 mo) and end-treatment (6 mo). All reported P values were based on two-sided tests and compared to a significance level of 5% (P < 0.05).
RESULTS
Patients’ characteristics
The screening visit was carried out on 82 potential participants, out of which 36 excluded and 46 recruited. All patients were Italian and Caucasian ethnicity. Table 1 summarizes characteristics of patients recruited for the study in terms of gender, age, anthropometry, BMI and steatosis grade, components of MS[39], MedDietScore,
physical activity and smoking habits.
Table 2 focuses on 12 patients with MS showing the number of patients affected by each component. At the moment of the inclusion in the study, 5 out of 12 patients with MS were under treatment for one or more components of the MS (5 for hypertension and 2 Gelli C et al. Mediterranean diet treatment for NAFLD
3155 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
also for dyslipidaemia) and 4 patients without MS were under treatment for the type 2 diabetes. In all cases the treatment was maintained unaltered throughout the study.
Effect of the treatment on steatosis grade, weight and
liver enzymes
At the baseline steatosis was grade 1 for 3 patients (7%), grade 2 for 19 patients (41%) and grade 3 for 24 patients (52%). At the end of the treatment steatosis was regressed in 9 patients (20%), 15 patients had a grade 1 (33%), 18 patients a grade 2 (39%) and only 4 patients still had a grade 3 (9%). Distribution of patients among steatosis grade at baseline and end-treatment is shown in Figure 1. Percentage of patients with severe steatosis was slightly higher than 50% at baseline and below 10% after the treatment.
At baseline 35 patients were overweight (BMI > 25) and 11 had normal weight. At the end of the treatment patients with a normal weight increased to 20. Among patients overweight at baseline, 12 achieved a weight reduction of at least 7% and in 7 cases it was reached a normal weight. At the end of the treatment the end-point concerning the weight was accomplished by 25 out of 46 patients (i.e., 54.3%).
As far as the liver enzymes is concerned, Figure 2 shows the percentage of abnormal values at BL, at mid-intervention (3M) and end-intervention (6M). All three liver enzymes significantly decrease during the treatment (see Table 3) and the reduction of abnormal values was elevated. The normalization was particularly evident for the ALT enzyme whose altered values reduced from 67% at baseline down to 11% after the treatment.
Table 3 summarizes results of the statistical analysis carried out in order to assess the effect of the treatment on anthropometric, clinical and metabolic parameters considered in this study.
Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, LDL, HDL, TG, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, QUICKI, FLI and LAP, showed a significant improvement between baseline and end-treatment. Among parameters positively affected by the treatment after 6 mo, most of them, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, serum glucose, Tot-Chol/HDL, LDL/HDL, HOMA, QUICKI, FLI and LAP (men) showed a significant improvement also after 3 mo from the start of the treatment.
In order to evaluate the efficacy of the approach proposed in this study for the management of NAFLD, the achievement of set end-points was evaluated. Figure 3 shows the percentage of patients that achieved the target, singularly for each end-points.
All criteria were achieved for at least 50% of patients. The percentage of success is particularly high (more than 80%) for steatosis, ALT, AST and GGT.
The intervention was also successful in increasing the percentage of participants carrying out physical activity on a regular basis (about 49% at baseline and 60% at end-intervention, Figure 4). Moreover, also people not able to carry out physical activity due to physical constraints declared their engagement
Gelli C et al. Mediterranean diet treatment for NAFLD
Table 1 Main characteristics of 46 patients recruited for the study Parameter Value (mean ± SD or frequency) Population n (%) Total 46 M 29 (63%) F 17 (37%) Age (yr) Range 26-71 mean ± SD 47.5 ± 12 BMI (kg/m2) Range 18.9-45.3 mean ± SD 29.3 ± 6.1 BMI (kg/m2) Obesity grade 18.5-24.9 (normal weight) 23.90% 25-29.9 (overweight) 43.50% 30-34.9 (class Ⅰ obesity) 17.40% 35-39.9 (class Ⅱ obesity) 8.70% ≥ 40 (class Ⅲ obesity) 6.50% Waist circumference (cm) M 100.88 ± 12.97 F 101.88 ± 15.07
Obesity central (Waist circumference)
M (> 102 cm) 48.30% F (> 88 cm) 82.40% Waist-to-hip ratio Android obesity M (≥ 1) 41.40% F (≥ 0.85) 70.60% Gynoid obesity M (≤ 0.94) 20.70% F (≤ 0.78) 0.00% Components of MS2 0 4 (8.7%) 1 20 (43.5%) 2 10 (21.7%) 3 5 (10.9%) 4 5 (10.9%) 5 2 (4.3%)
Liver steatosis grade
1 3 (6.5%) 2 19 (41.3%) 3 24 (52.2%) MedDiet Score Range 21-41 mean ± SD 28.4 ± 3.9 Physical activity No 24 (52.2%) Yes 22 (47.8%) Times1/wk 1 6 (13%) 2 7 (15.2%) 3 7 (15.2%) > 3 2 (4.3%) Smoking No 35 (76.1%) Ex 3 (6.5%) Yes 8 (17.4%)
3156 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
in increasing their physical activity through simple daily activities indicated in the section concerning the counseling process.
Table 4 shows the correlations between steatosis grade and anthropometric, clinical and metabolic parameters considered in this study.
Only waist-to-hip ratio and HOMA correlated with steatosis grade both at baseline and at end-treatment. Some parameters, e.g., BMI, waist circumference, serum glucose and QUICKI, didn’t show any significant correlation at baseline but the correlation was ob-served at end-treatment. Other parameters, e.g., Total Cholesterol, HDL, AST/ALT and PLr, showed a tendency only at the end- treatment.
Table 5 shows the correlations between BMI and anthropometric, clinical and metabolic parameters considered in this study.
Some parameters, i.e., waist circumference, MS, HOMA-Ir, QUICKI, Kotronen index, NAFLD liver fat score, and LAP (male) correlated with BMI both at baseline and at end-treatment. Some parameters,
i.e., hip-to-waist ratio, Tot. Chol., HDL didn’t show any
significant correlation at baseline but the correlation was observed at end-treatment. On the other hand, FLI and BARD, showed a significant correlation only at baseline. Correlation between BMI and steatosis grade was previously reported, while correlation between BMI and MedDiet score is significant but is available only at baseline.
DISCUSSION
Most recent advances in the management and treat-ment of NAFLD show that a multifaceted approach, using a multidisciplinary team is likely to achieve the best outcome[40]. Combination of physical activity,
medications, and dietetic interventions can be more effective than each prescription alone[24]. In addition,
intervention tailored and aimed at encouraging self-empowerment and behavioral change are regarded as essential for increasing adhesion to treatments[40].
This observational study is set in this research trend and was aimed at evaluating the effectiveness of a 6-mo multidisciplinary approach jointly carried out by a gastroenterologist and a nutritionist with counseling license for treating patients with NAFLD. The nutritional counseling was used as tool for encouraging patients to improve their lifestyle (MedDiet-based dietary habits and regular physical activity).
According to our results, the approach clearly demonstrated its effectiveness on reduction of NAFL severity, weight loss and anthropometric indexes as well as normalization of metabolic index and liver enzymes.
Some patients’ characteristics at baseline are of relevance for discussing the results obtained. Firstly, it is interesting to point out that the MedDiet score is similar to that reported by Kontogianni et al[21]
(28.4 ± 3.9 in this study and 32.5 ± 5.0 in the other study). According to our results the MedDietScore was significantly and inversely correlated with steatosis grade (P = 0.044) (Table 4).
Also, a significant percentage of patients (about 25%) had normal weight confirming that, even if positive energy balance and increased BMI sub-stantially increase the risk of NAFLD, this latter may develop in individuals with normal BMI as well[41] e.g.,
as a consequence of an uncorrected lifestyle.
It is also interesting to underline that BMI and waist circumference does not correlate with NAFLD grade at baseline but correlation is significant at end-treatment for both parameters. At baseline, patients were also characterized by altered insulin resistance (Ir) and
Table 2 Frequency of metabolic syndrome’ components in patients with metabolic syndrome
Component Hypertension Blood pressure TG HDL Serum glucose
n 12 6 12 7 8
TG: Triglycerides; HDL: High-density lipoprotein.
100.0 80.0 60.0 40.0 20.0 0.0 BL 3M 6M BL 3M 6M BL 3M 6M AST ALT GGT 26.1 (%) 73.9 19.6 80.4 8.7 91.3 67.4 32.6 28.3 71.7 10.9 89.1 34.8 65.2 21.7 78.3 17.4 82.6 Abnormal values Normal values
Figure 2 Effect of the treatment on the normalization of liver enzymes.
Normal values: < 40 U/L for AST, < 50 U/L for ALT, < 55 U/L for GGT. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase.
Gelli C et al. Mediterranean diet treatment for NAFLD
100 80 60 40 20 0 % Baseline 6M Severe Moderate Mild Absent
Figure 1 Steatosis grade of patients at baseline and end-treatment.
52 41 7 9 33 20 39
3157 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
insulin sensitivity, respectively estimated by HOMA-Ir and QUICKI, as could be expected considering that Ir is usually associated to NAFLD[12] and recently
identified as the key aspect in the pathophysiology of both NAFLD and MS[42].
The reduction of NAFLD severity of patients is the main and relevant outcome of the treatment. In fact, the effects of MedDiet and increased physical activity, both associated or separated, have been investigated in several studies in terms of NAFLD-related indexes[37],
hepatic enzymes[43], reduction of cardiovascular risk[44]
or improvement in insulin sensitivity[45]. However, the
present observational study is the first specifically examining effects of a multidisciplinary approach aimed at promoting the adherence to MedDiet and an active lifestyle directly on NAFLD severity.
According to Figure 3, in more than 80% of patients at least one grade reduction of NAFLD severity was observed. Our results confirm the positive outcomes of the study carried out by ryan et al[46] who observed a
Table 3 Anthropometric, clinical and metabolic parameters at baseline, mid-intervention (3M) and end-intervention (6M) and results of the statistical analysis
Parameter mean ± SD, BL mean ± SD, 3M mean ± SD, 6M P value
BL vs 3M 3M vs 6M BL vs 6M BMI (kg/m2) 29.3 ± 6.11 28.0 ± 6.21 27.5 ± 6.21 < 0.01a < 0.01a < 0.01a Waist circumference (cm) 101.25 ± 13.63 97.50 ± 14.07 96.24 ± 13.64 < 0.01a < 0.01a < 0.01a Hip-to-waist ratio 0.95 ± 0.08 0.94 ± 0.07 0.93 ± 0.08 < 0.01a < 0.01a < 0.01a AST (U/L) 36.16 ± 21.11 28.73 ± 11.28 24.84 ± 10.70 < 0.01a < 0.01a < 0.01a ALT (U/L) 65.66 ± 31.92 48.37 ± 33.44 37.33 ± 19.53 < 0.01a < 0.01a < 0.01a GGT (U/L) 60.19 ± 61.43 41.35 ± 36.49 39.73 ± 35.36 < 0.01a 0.545 < 0.01a FA (U/L) 81.48 ± 37.19 79.54 ± 32.04 80.04 ± 35.02 0.489 0.787 0.574 Total cholesterol (mg/dL) 215.24 ± 40.78 205.04 ± 41.75 207.18 ± 38.48 0.044a 0.598 0.097 LDL cholesterol (mg/dL) 137.70 ± 32.87 131.25 ± 35.88 130.16 ± 32.65 0.071 0.941 0.050a HDL cholesterol (mg/dL) 49.72 ± 10.59 50.17 ± 11.64 53.09 ± 11.86 0.550 < 0.01a < 0.01a TG (mg/dL) 133.39 ± 67.77 123.65 ± 71.31 118.24 ± 65.14 0.112 0.358 0.017a Serum glucose (mg/dL) 98.33 ± 15.87 94.52 ± 13.07 95.76 ± 13.46 < 0.01a 0.133 < 0.01a Chol Tot/HDL 4.50 ± 1.27 4.23 ± 1.07 3.95 ± 1.15 0.013a 0.010a < 0.01a LDL/HDL 2.89 ± 0.95 2.67 ± 0.93 2.56 ± 0.84 0.028a 0.015a < 0.01a TG/HDL 2.87 ± 1.76 2.66 ± 1.89 2.39 ± 1.66 0.152 0.037a < 0.01a AIP 0.03 ± 0.25 -0.01 ± 0.23 -0.06 ± 0.25 0.097 0.089 < 0.01a HOMA- IR (mU/L) 3.25 ± 1.96 2.96 ± 1.73 2.94 ± 1.67 < 0.01a 0.841 < 0.01a QUICKI 0.33 ± 0.04 0.34 ± 0.04 0.34 ± 0.03 < 0.01a 0.330 < 0.017a PLR 115.37 ± 46.60 109.89 ± 51.77 113.65 ± 43.77 0.195 0.281 0.816 NLR 1.98 ± 1.12 1.88 ± 1.10 1.79 ± 0.89 0.287 0.509 0.185 FLI 61.55 ± 26.76 50.54 ± 29.37 48.83 ± 31.01 < 0.01a 0.286 < 0.01a Kotronen index (%) 6.05 ± 5.02 4.10 ± 2.22 3.92 ± 2.40 < 0.01a 0.277 < 0.01a VAI 1.85 ± 1.17 1.55 ± 0.71 1.32 ± 0.65 0.011 0.010 < 0.01a NAFLD Liver Fat Score 0.12 ± 1.63 -0.02 ± 1.42 -0.70 ± 1.20 0.418 < 0.01a < 0.01a LAP (male) 48.41 ± 28.14 37.01 ± 19.95 33.18 ± 17.49 < 0.01a 0.166 < 0.01a LAP (female) 84.15 ± 63.06 78.92 ± 70.51 74.13 ± 58.89 0.290 0.452 < 0.01a BARD 1.09 ± 1.26 1.46 ± 1.17 1.37 ± 1.04 0.011a 0.486 0.091 NAFLD -2.29 ± 0.93 -2.13 ± 1.01 -2.28 ± 1.00 0.015a 0.032a 0.986 Values are expressed as mean ± SD. aP ≤ 0.05, significant difference. BL: Baseline; NAFLD: Non-alcoholic fatty liver disease; TG: Triglycerides; HDL: High-density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase.
100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 End-point achievement (%) Steatosis grade Weight Serum glucose
Tot-Col LDL-Col HDL-Col Serum TG AST ALT GGT 80.4 54.3 50.0 67.4 58.7 52.2 71.7 87.0 89.1 91.3
Figure 3 Grade of success for parameters and measures included in the end-points. TG: Triglycerides; HDL: Highdensity lipoprotein; AST: Aspartate
aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase.
3158 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
Table 4 Correlation between steatosis grade and anthropometric, clinical and metabolic parameters considered in this study at baseline and at end-treatment
Parameter Grade 0 (n = 9) Grade I (n = 15) Grade 2 (n = 18) Grade 3 (n = 4) P value mean ± STD mean ± STD mean ± STD mean ± STD
BMI (kg/m2) BL - 30.19 ± 2.15 28.05 ± 6.47 30.11 ± 6.14 0.499 6M 23.39 ± 3.52 25.94 ± 5.60 31.36 ± 6.53 25.77 ± 1.14 0.013a Waist circumference (cm) BL - 103.00 ± 1.73 96.05 ± 12.94 105.15 ± 13.91 0.122 6M 86.44 ± 11.98 90.73 ± 9.24 106.03 ± 12.64 94.88 ± 9.37 < 0.01a Hip-to-waist ratio (-) BL - 0.94 ± 0.05 0.91 ± 0.08 0.98 ± 0.07 0.020a 6M 0.88 ± 0.06 0.91 ± 0.06 0.97 ± 0.08 0.93 ± 0.09 < 0.01a Tot Chol (mg/dL) BL - 260.67 ± 27.21 210.95 ± 31.20 212.96 ± 46.24 0.266 6M 215.89 ± 39.78 196.27 ± 62.92 212.06 ± 34.35 154.75 ± 44.90 0.078 HDL (mg/dL) BL - 47.00 ± 3.46 52.05 ± 13.39 48.21 ± 8.39 0.532 6M 142.16 ± 33.53 130.60 ± 22.94 131.33 ± 35.27 96.25 ± 38.88 0.070 LDL (mg/dL) BL - 186.67 ± 37.63 133.52 ± 19.00 134.88 ± 37.05 0.119 6M 54.33 ± 12.97 53.73 ± 14.08 53.56 ± 10.74 45.75 ± 1.89 0.399 TG (mg/dL) BL - 134.00 ± 43.28 125.21 ± 42.18 139.79 ± 85.63 0.597 6M 100.22 ± 31.69 119.20 ± 40.40 138.22 ± 88.51 65.25 ± 42.94 0.807 AST BL - 0.72 ± 0.28 0.87 ± 0.33 0.95 ± 0.67 0.435 6M 0.55 ± 0.15 0.63 ± 0.19 0.67 ± 0.37 0.53 ± 0.17 0.641 ALT BL - 0.91 ± 0.20 1.32 ± 0.68 1.35 ± 0.64 0.419 6M 0.56 ± 0.14 0.79 ± 0.37 0.82 ± 0.50 0.67 ± 0.23 0.334 AST/ALT BL - 0.76 ± 0.15 0.71 ± 0.19 0.66 ± 0.20 0.276 6M 0.95 ± 0.15 0.76 ± 0.22 0.73 ± 0.26 0.78 ± 0.11 0.058 GGT BL - 58.67 ± 64.53 51.89 ± 54.69 42.21 ± 25.60 0.392 6M 17.00 ± 4.12 43.53 ± 25.67 44.39 ± 0.10 27.25 ± 0.50 0.147 Blood gluc. (mg/dL) BL - 96.67 ± 9.29 94.16 ± 15.71 101.83 ± 16.26 0.181 6M 88.00 ± 1.94 91.27 ± 7.33 104.33 ± 17.03 91.50 ± 8.19 0.018a SM (n) BL - 2.67 ± 1.15 1.32 ± 1.00 2.17 ± 1.43 0.350 6M 1.44 ± 1.13 1.73 ± 1.28 2.28 ± 1.49 1.25 ± 0.50 0.415 Tot-Chol/HDL BL - 5.60 ± 1.03 4.29 ± 1.27 4.53 ± 1.26 0.637 6M 4.07 ± 0.84 3.84 ± 1.55 4.09 ± 0.94 3.41 ± 1.09 0.479 LDL/HDL BL - 4.03 ± 1.14 2.72 ± 0.82 2.88 ± 0.96 0.355 6M 2.70 ± 0.82 2.60 ± 0.90 2.54 ± 0.82 2.12 ± 0.91 0.333 TG/HDL BL - 2.83 ± 0.78 2.63 ± 1.36 3.07 ± 2.11 0.516 6M 1.92 ± 0.73 2.44 ± 1.25 2.79 ± 2.24 1.46 ± 1.02 0.698 AIP BL - 0.44 ± 0.11 0.37 ± 0.21 0.39 ± 0.29 0.983 6M 0.25 ± 0.19 0.34 ± 0.21 0.35 ± 0.27 0.08 ± 0.31 0.780 HOMA-IR (mU/L) BL - 2.77 ± 0.22 2.37 ± 1.37 4.01 ± 2.18 0.015a 6M 1.50 ± 0.84 2.47 ± 1.06 4.12 ± 1.71 2.67 ± 1.51 < 0.01a QUICKI BL - 0.33 ± 0.00 0.35 ± 0.04 0.32 ± 0.03 0.082 6M 0.37 ± 0.05 0.34 ± 0.02 0.32 ± 0.02 0.34 ± 0.03 < 0.01a PLR BL - 120.89 ± 28.83 107.31 ± 32.51 121.06 ± 57.08 0.467 6M 93.44 ± 22.18 106.95 ± 48.08 127.33 ± 47.95 122.70 ± 30.46 0.058 NLR BL - 1.36 ± 0.37 1.79 ± 0.80 2.21 ± 1.34 0.112 6M 1.32 ± 0.21 1.67 ± 1.08 2.21 ± 0.85 1.44 ± 0.50 0.097 FLI BL - 98.97 ± 0.30 98.84 ± 0.39 98.70 ± 0.75 0.612 6M 98.48 ± 0.72 98.79 ± 0.40 98.75 ± 0.67 97.08 ± 1.82 0.143 Kotronen index (%) BL - 4.63 ± 2.14 4.3 ± 2.0 7.6 ± 6.4 0.047a 6M 2.15 ± 0.83 3.5 ± 1.0 5.3 ± 3.2 3.1 ± 0.6 0.017a VAI BL - 3.5 ± 1.8 1.9 ± 1.0 1.6 ± 1.1 0.041a 6M 1.44 ± 0.64 1.38 ± 0.65 1.29 ± 0.67 0.9 ± 0.67 0.224 NAFLD fat liver score BL - -0.42 ± 0.9 -0.6 ± 1.1 0.7 ± 1.8 0.016a
6M 1.88 ± 0.71 -0.84 ± 0.78 0.07 ± 1.27 -0.99 ± 0.63 < 0.01a LAP (male) BL - 52.00 ± 0.00 44.27 ± 19.98 50.51 ± 32.82 0.694 6M 25.67 ± 11.38 31.11 ± 14.62 42.38 ± 19.13 26.11 ± 22.32 0.386 LAP (female) BL - 72.10 ± 32.56 56.13 ± 31.50 130.21 ± 83.11 0.377 6M 24.42 ± 16.25 52.21 ± 23.70 109.22 ± 67.63 - 0.147 BARD BL - 2.33 ± 1.15 0.79 ± 1.08 1.17 ± 1.34 0.733 6M 1.89 ± 0.33 1.07 ± 1.03 1.56 ± 1.15 0.50 ± 1.00 0.192 NAFLD BL - -3.41 ± 0.48 -2.25 ± 0.73 -2.17 ± 1,02 0.112 6M -2.44 ± 0.93 -2.68 ± 0.87 -1.88 ± 1.07 -2.27 ± 0.91 0.144 MedDiet Score BL - 30.0 ± 3.0 29.6 ± 4.6 27.2 ± 3.1 0.044a 6M NA NA NA NA NA
aP ≤ 0.05, significant difference. NAFLD: Non-alcoholic fatty liver disease; TG: Triglycerides; HDL: High-density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase.
3159 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
positive effect of MedDiet on NAFLD. However, results cannot be directly compared due to the different method used to assess NAFLD severity.
The treatment showed positive effects on anthro-pometric indexes. In fact BMI decreased on average from 29.3 ± 6.11 to 27.5 ± 6.21, waist circumference decreased on average from 101.25 ± 13.63 to 96.24 ± 13.64 and hip-to-waist ratio decreased on average from 0.95 ± 0.08 to 0.93 ± 0.08 (Table 3). The improvement of previous anthropometric indexes is of relevance considering that all of them impact on CVD and MS related states and risks.
Excellent results of the treatment was confirmed
also by the significant reduction of the Kotronen index (by 35% of the average and P < 0.01), the VAI (by 28% of the average and P < 0.01), NAFLD liver fat score (by 18% of the average and P < 0.01) and FLI (by 21% of the average and P < 0.01) (Table 3). Steatosis grade resulted significantly correlated with Kotronen index and NAFLD liver fat score both at baseline and end-treatment while correlation of steatosis grade with VAI was significant only at baseline. Absence of correlation at end-treatment could be due to the significant number of patients which showed regression of the disease. On the contrary the index FLI did not correlate with steatosis grade neither at baseline nor at end-treatment.
During the 6-mo of the treatment was also ob-served an improvement of the lipid profile of several patients (Figure 3). In fact, considering mean values, it was observed a reduction of Tot-Chol (215.24 ± 40.78
vs 207.18 ± 38.48), LDL (137.70 ± 32.87 vs 130.16
± 32.65) and TG (133.39 ± 67.77 vs 118.24 ± 65.14) while an increase was observed for HDL (49.72 ± 10.59 vs 53.09 ± 11.86) (Table 3).
The treatment had also positive effects on liver enzymes with improvements or normalization of AST (36.16 ± 21.11 at baseline and 24.84 ± 10.70 at end-treatment), ALT (65.66 ± 31.92 at baseline and 37.33 ± 19.53 at end-treatment) and GGT (60.19 ± 61.43 at
Table 5 Correlation between BMI and anthropometric, clinical and metabolic parameters considered in this study at baseline and at end-treatment
Parameter P value Parameter P value
Steatosis grade BL 0.499 TG/HDL BL 0.370
6M 0.013a 6M 0.416
Waist circumf. (cm) BL < 0.01a AIP BL 0.194
6M < 0.01a 6M 0.307
Hip-to-waist ratio (-) BL 0.231 HOMA-IR (mU/L) BL < 0.01a
6M 0.020a 6M < 0.01a
Tot Chol (mg/dL) BL 0.257 QUICKI BL < 0.01a
6M < 0.01a 6M < 0.01a HDL (mg/dL) BL 0.255 PLR BL 0.213 6M < 0.01a 6M 0.645 LDL (mg/dL) BL 0.211 NLR BL 0.066 6M 0.768 6M 0.167 TG (mg/dL) BL 0.352 FLI BL < 0.01a 6M 0.229 6M 0.137
AST BL 0.244 Kotronen index (%) BL 0.038a
6M 0.093 6M < 0.01a
ALT BL 0.504 VAI BL 0.479
6M 0.154 6M 0.373
AST/ALT BL 0.195 NAFLD fat liver score BL < 0.01a
6M 0.114 6M < 0.01a
GGT BL 0.075 LAP (male) BL < 0.01a
6M 0.176 6M < 0.01a
MS (n) BL 0.025a LAP (female) BL 0.075
6M 0.025a 6M 0.176
Blood gluc. (mg/dL) BL 0.182 BARD BL < 0.01a
6M 0.142 6M 0.079
Tot-Chol/HDL BL 0.218 NAFLD BL 0.058
6M 0.090 6M 0.167
LDL/HDL BL 0.185 MedDiet Score BL 0.049a
6M 0.087 6M NA
aP ≤ 0.05, significant difference. TG: Triglycerides; HDL: High-density lipoprotein.
Gelli C et al. Mediterranean diet treatment for NAFLD
Figure 4 Percentage of participants carrying out physical activity on a regular basis at baseline and at end-intervention.
100 90 80 70 60 50 40 30 20 10 0 BL 6M % Yes No 48 52 60 40
3160 May 7, 2017|Volume 23|Issue 17|
WJG|www.wjgnet.com
baseline and 39.73 ± 35.36 at end-treatment) (Table 3 and Figure 3). Of particular relevance was the effect on ALT with altered values reduced from almost 70% at baseline to just 10% at end-treatment. Normalization of values was significant also for AST (altered values at baseline were three-fold those at end treatment) and GGT (altered values were halved at end-treatment).
Positive effects of the MedDiet on liver enzymes were already observed by Fraser et al[43] in obese
patients with type 2 diabetes and in the ATTICA study, that evaluated the prevalence of MS among over 3000 Greek adults[47]. On the other hand it is interesting to
point out that ryan et al[46] observed a positive effect
of MedDiet on reduction in liver fat content (assessed with magnetic resonance imaging) but no significant differences in AST and ALT values were observed.
The treatment also showed positive effects on insulin resistance and insulin sensitivity: HOMA-Ir significantly reduce at end-treatment with respect to baseline (3.25 ± 1.96 vs 2.94 ± 1.67, P < 0.01) while QUICKI increase (0.33 ± 0.04 vs 0.34 ± 0.03). Considering the reduction observed for the NAFLD grade, this result was expected, as NAFLD worsens the state of Ir and may lead on to type 2 diabetes in the predisposed subjects[48]. Improvement of Ir was
expected considering that it was already observed in previous studies as a consequence of treatment centered either on MedDiet[46] or increased physical
activity[37].
In conclusions, outcomes of this study further strengthen the hypothesis that MedDiet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states such as MS and CVD. This suggests that the proposed approach, carried out by a multidisciplinary team composed of a gastro-enterologist and a nutritionist with counseling license, may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.
Although this study does not allow to assess the effect of nutritional counseling, excellent results in terms end-points achievement (Figure 3) suggest that the adherence to the proposed approach was very successful.
replication and improvement of the study design, by a control arm and a follow-up after the end-treatment, are advisable to confirm the outcomes obtained so far and to assess the importance of multidisciplinary and counseling in modern approach for clinical management of NAFLD.
Limitations of the study
In this study we did not distinguish between simple fatty liver and NASH. In addition, despite Mr-S is considered gold standards for assessing the severity of NAFLD using non-invasive techniques, in this study was used US which is considered the preferred first-line diagnostic procedure for imaging (EASL-EASD-EASO, 2016). According to previous studies (inter alia
Ghaemi et al[49], 2013) we also supported the diagnosis
with US with serum biomarkers and scores.
COMMENTS
Background
Non-alcoholic fatty liver disease (NAFLD) is a relevant issue in public health because represents a major cause of chronic liver diseases worldwide. Approximately 20% to 30% of adult population has NAFLD, making it the most common liver disease in developed countries. Most recent advances in the management and treatment of NAFLD show that a multifaceted approach to improve lifestyle is likely to achieve the best outcomes.
Research frontiers
These results indicate the possibility of using lifestyle change, based on MetDiet and constant physical activity, as a powerful tool for treating dismetabolic diseases and only in some cases is required pharmacological treatments.
Innovations and breakthroughs
In this work the authors demonstrate that MedDiet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The real novelty was the double approach carried out respectively by a gastroenterologist and a nutritionist with counseling license.
Applications
This research focuses on the improvement of the therapy of patients with NAFLD but our results indicate that this double approach can be used also to increase adherence to diet or therapy of general patients.
Terminology
NAFLD is an important liver disease worldwide generally associated with the Metabolic Syndrome. In this study to achieve an improvement in these patients an important treatment method based on life-style modification and Mediterranean diet (MetDiet) was achieved through a multidisciplinary approach jointly carried out by a gastroenterologist and a nutritionist with counseling license.
Peer-review
The study discusses an approach for treatment NAFLD which is an important liver disease worldwide. The study is well written and interesting. The study focused on an important treatment method based on lifestyle modification and diet control.
REFERENCES
1 Wah-Kheong C, Khean-Lee G. Epidemiology of a fast emerging
disease in the Asia-Pacific region: non-alcoholic fatty liver disease. Hepatol Int 2013; 7: 65-71 [PMID: 26201622 DOI: 10.1007/ s12072-012-9384-1]
2 Papamiltiadous ES, Roberts SK, Nicoll AJ, Ryan MC,
Itsiopoulos C, Salim A, Tierney AC. A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): study protocol. BMC Gastroenterol 2016; 16: 14 [PMID: 26831892]
3 Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A
position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010; 53: 372-384 [PMID: 20494470 DOI: 10.1016/j.jhep.2010.04.008]
4 European Association for the Study of the Liver (EASL);
European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64: 1388-1402 [PMID: 27062661 DOI: 10.1016/j.jhep.2015.11.004]
5 Levene AP, Goldin RD. The epidemiology, pathogenesis and
